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  1. Artikel ; Online: Potential of HMGB-inhibitory oligodeoxynucleotide ISM ODN to neutrophil recruitment in mouse model of hepatitis.

    Inoue, Asuka / Chiba, Shiho / Eto, Shotaro / Taniguchi, Tadatsugu / Yanai, Hideyuki

    Genes to cells : devoted to molecular & cellular mechanisms

    2022  Band 28, Heft 3, Seite(n) 202–210

    Abstract: High-mobility group box 1 (HMGB1) is a nucleotide-binding chromatin protein that has also been characterized as a prototypical damage-associate molecular pattern. It triggers inflammatory responses upon release from damaged or dying cells. In fact, HMGB1 ...

    Abstract High-mobility group box 1 (HMGB1) is a nucleotide-binding chromatin protein that has also been characterized as a prototypical damage-associate molecular pattern. It triggers inflammatory responses upon release from damaged or dying cells. In fact, HMGB1 has been linked to the induction of many inflammatory diseases through immune cell activation including neutrophil recruitment. In this study, we examined the impact of HMGB1-binding inhibitory oligodeoxynucleotide (ISM ODN) on the development of hepatitis using a murine model of the disease. Our results indicate that ISM ODN effectively suppresses pathological features of hepatitis, including neutrophil accumulation. This study therefore may offer clinical insight into the treatment of hepatitis and possibly other inflammatory diseases.
    Mesh-Begriff(e) Mice ; Animals ; HMGB1 Protein/metabolism ; Oligodeoxyribonucleotides/pharmacology ; Disease Models, Animal ; Neutrophil Infiltration ; Hepatitis
    Chemische Substanzen HMGB1 Protein ; Oligodeoxyribonucleotides
    Sprache Englisch
    Erscheinungsdatum 2022-12-27
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 1330000-3
    ISSN 1365-2443 ; 1356-9597
    ISSN (online) 1365-2443
    ISSN 1356-9597
    DOI 10.1111/gtc.13002
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Signal-transducing innate receptors in tumor immunity.

    Hangai, Sho / Kimura, Yoshitaka / Taniguchi, Tadatsugu / Yanai, Hideyuki

    Cancer science

    2021  Band 112, Heft 7, Seite(n) 2578–2591

    Abstract: The signal-transducing innate receptors represent classes of pattern recognition receptors (PRRs) that play crucial roles in the first line of the host defense against infections by the recognition of pathogen-derived molecules. Because of their poorly ... ...

    Abstract The signal-transducing innate receptors represent classes of pattern recognition receptors (PRRs) that play crucial roles in the first line of the host defense against infections by the recognition of pathogen-derived molecules. Because of their poorly discriminative nature compared with antigen receptors of the adaptive immune system, they also recognize endogenous molecules and evoke immune responses without infection, resulting in the regulation of tumor immunity. Therefore, PRRs may be promising targets for effective cancer immunotherapy, either by activating or inhibiting them. Here, we summarize our current knowledge of signal-transducing PRRs in the regulation of tumor immunity.
    Mesh-Begriff(e) Animals ; Cell Membrane/metabolism ; Cytoplasm/metabolism ; Humans ; Immunity, Innate ; Immunotherapy/trends ; Neoplasms/immunology ; Neoplasms/therapy ; Receptors, Pattern Recognition/immunology ; Receptors, Pattern Recognition/metabolism ; Signal Transduction/immunology ; Tumor Microenvironment/immunology
    Chemische Substanzen Receptors, Pattern Recognition
    Sprache Englisch
    Erscheinungsdatum 2021-05-01
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2115647-5
    ISSN 1349-7006 ; 1347-9032
    ISSN (online) 1349-7006
    ISSN 1347-9032
    DOI 10.1111/cas.14848
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel: [Regulation of innate immune responses by nucleic acid analogues].

    Yanai, Hideyuki

    Uirusu

    2012  Band 61, Heft 2, Seite(n) 141–152

    Abstract: The activation of innate immune responses by nucleic acids is critical to host responses against pathogens, such as viruses; however, nucleic acids can also trigger the development and/or exacerbation of pathogenic responses such as autoimmunity. We ... ...

    Abstract The activation of innate immune responses by nucleic acids is critical to host responses against pathogens, such as viruses; however, nucleic acids can also trigger the development and/or exacerbation of pathogenic responses such as autoimmunity. We previously demonstrated that the selective activation of nucleic acid-sensing cytosolic and Toll-like receptors is contingent on the promiscuous sensing of nucleic acids by high-mobility group box proteins (HMGBs). Basides these findings, we also found that nonimmunogenic nucleotide with high-affinity HMGB binding, termed ISM ODN, functions as suppressing agent for nucleic acid-activated innate immune responses. In this review, we aim to summerize this novel feature of HMGB proteins in nucleic acid-mediated innate immune responses. In addition, we will discuss the inhibitory effect of nonimmunogenic oligodeoxynucleotides (ni-ODNs) targeting HMGB proteins.
    Mesh-Begriff(e) Autoimmune Diseases/immunology ; HMGB Proteins/physiology ; Humans ; Immunity, Innate/immunology ; Immunomodulation ; Nucleic Acids/physiology ; Oligodeoxyribonucleotides/immunology ; Receptors, Pattern Recognition/physiology ; Signal Transduction/physiology ; Toll-Like Receptors/physiology
    Chemische Substanzen HMGB Proteins ; Nucleic Acids ; Oligodeoxyribonucleotides ; Receptors, Pattern Recognition ; Toll-Like Receptors
    Sprache Japanisch
    Erscheinungsdatum 2012-07-15
    Erscheinungsland Japan
    Dokumenttyp English Abstract ; Journal Article ; Review
    ZDB-ID 603272-2
    ISSN 0042-6857
    ISSN 0042-6857
    DOI 10.2222/jsv.61.141
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Damage-associated molecular patterns and Toll-like receptors in the tumor immune microenvironment.

    Yanai, Hideyuki / Hangai, Sho / Taniguchi, Tadatsugu

    International immunology

    2020  Band 33, Heft 12, Seite(n) 841–846

    Abstract: As clinically demonstrated by the success of immunotherapies to improve survival outcomes, tumors are known to gain a survival advantage by circumventing immune surveillance. A defining feature of this is the creation and maintenance of a tumor immune ... ...

    Abstract As clinically demonstrated by the success of immunotherapies to improve survival outcomes, tumors are known to gain a survival advantage by circumventing immune surveillance. A defining feature of this is the creation and maintenance of a tumor immune microenvironment (TIME) that directly and indirectly alters the host's immunologic signaling pathways through a variety of mechanisms. Tumor-intrinsic mechanisms that instruct the formation and maintenance of the TIME have been an area of intensive study, such as the identification and characterization of soluble factors actively and passively released by tumor cells that modulate immune cell function. In particular, damage-associated molecular pattern (DAMP) molecules typically released by necrotic tumor cells are recognized by innate immune receptors such as Toll-like receptors (TLRs) and stimulate immune cells within TIME. Given their broad and potent effects on the immune system, a better understanding for how DAMP and TLR interactions sculpt the TIME to favor tumor growth would identify new strategies and approaches for cancer immunotherapy.
    Mesh-Begriff(e) Animals ; Humans ; Neoplasms/immunology ; Toll-Like Receptors/immunology ; Tumor Microenvironment/immunology
    Chemische Substanzen Toll-Like Receptors
    Sprache Englisch
    Erscheinungsdatum 2020-09-29
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1013745-2
    ISSN 1460-2377 ; 0953-8178
    ISSN (online) 1460-2377
    ISSN 0953-8178
    DOI 10.1093/intimm/dxab050
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Tumor cell-derived spermidine is an oncometabolite that suppresses TCR clustering for intratumoral CD8

    Hibino, Sana / Eto, Shotaro / Hangai, Sho / Endo, Keiko / Ashitani, Sanae / Sugaya, Maki / Osawa, Tsuyoshi / Soga, Tomoyoshi / Taniguchi, Tadatsugu / Yanai, Hideyuki

    Proceedings of the National Academy of Sciences of the United States of America

    2023  Band 120, Heft 24, Seite(n) e2305245120

    Abstract: The activation and expansion of T cells that recognize cancer cells is an essential aspect to antitumor immunity. Tumors may escape destruction by the immune system through ectopic expression of inhibitory immune ligands typically exemplified by the PD- ... ...

    Abstract The activation and expansion of T cells that recognize cancer cells is an essential aspect to antitumor immunity. Tumors may escape destruction by the immune system through ectopic expression of inhibitory immune ligands typically exemplified by the PD-L1/PD-1 pathway. Here, we reveal another facet of tumor evasion from T cell surveillance. By secretome profiling of necrotic tumor cells, we identified an oncometabolite spermidine as a unique inhibitor of T cell receptor (TCR) signaling. Mechanistically, spermidine causes the downregulation of the plasma membrane cholesterol levels, resulting in the suppression of TCR clustering. Using syngeneic mouse models, we show that spermidine is abundantly detected in the tumor immune microenvironment (TIME) and that administration of the polyamine synthesis inhibitor effectively enhanced CD8
    Mesh-Begriff(e) Animals ; Mice ; Spermidine/pharmacology ; Spermidine/metabolism ; CD8-Positive T-Lymphocytes ; Neoplasms/metabolism ; Antineoplastic Agents/pharmacology ; Immunotherapy/methods ; Receptors, Antigen, T-Cell/metabolism ; Tumor Microenvironment ; Cell Line, Tumor ; B7-H1 Antigen/metabolism
    Chemische Substanzen Spermidine (U87FK77H25) ; Antineoplastic Agents ; Receptors, Antigen, T-Cell ; B7-H1 Antigen
    Sprache Englisch
    Erscheinungsdatum 2023-06-05
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2305245120
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Fine-tuning type I IFN signaling: A new chapter in the IFN saga.

    Yanai, Hideyuki / Taniguchi, Tadatsugu

    Cell research

    2017  Band 27, Heft 12, Seite(n) 1407–1408

    Abstract: Type I interferon (IFN) signaling is critical for intracellular antimicrobial programmes, affecting both innate and adaptive immune responses. The paper recently published in Cell demonstrates a new regulatory mechanism of the type I IFN signaling ... ...

    Abstract Type I interferon (IFN) signaling is critical for intracellular antimicrobial programmes, affecting both innate and adaptive immune responses. The paper recently published in Cell demonstrates a new regulatory mechanism of the type I IFN signaling pathway by histone-lysine N-methyltransferase SETD2.
    Mesh-Begriff(e) Antiviral Agents ; Histone-Lysine N-Methyltransferase ; Interferon Type I ; Methylation ; Signal Transduction
    Chemische Substanzen Antiviral Agents ; Interferon Type I ; Histone-Lysine N-Methyltransferase (EC 2.1.1.43)
    Sprache Englisch
    Erscheinungsdatum 2017-09-19
    Erscheinungsland England
    Dokumenttyp Journal Article ; Comment
    ZDB-ID 1319303-x
    ISSN 1748-7838 ; 1001-0602
    ISSN (online) 1748-7838
    ISSN 1001-0602
    DOI 10.1038/cr.2017.118
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: The impact of damage-associated molecules released from canine tumor cells on gene expression in macrophages.

    Eto, Shotaro / Yanai, Hideyuki / Hangai, Sho / Kato, Daiki / Nishimura, Ryohei / Nakagawa, Takayuki

    Scientific reports

    2021  Band 11, Heft 1, Seite(n) 8525

    Abstract: Dying or damaged cells that are not completely eradicated by the immune system release their intracellular components in the extracellular space. Aberrant exposure of the damage-associated molecules to the immune system is often associated with ... ...

    Abstract Dying or damaged cells that are not completely eradicated by the immune system release their intracellular components in the extracellular space. Aberrant exposure of the damage-associated molecules to the immune system is often associated with inflammation and cancer pathogenesis. Thus, elucidating the role of damage-associated molecules in inducing sterile immune responses is crucial. In this study, we show that prostaglandin E2 (PGE2) is produced in the supernatants from several types of canine necrotic tumor cell lines. Inhibition of PGE2 production by indomethacin, a potent inhibitor of cyclooxygenase (COX) enzymes, induces the expression of tumor necrosis factor (Tnf) mRNA in the necrotic tumor cell supernatants. These results comply with the previous observations reported in mouse cell lines. Furthermore, comprehensive ribonucleic acid-sequencing (RNA-seq) analysis revealed that three categories of genes were induced by the damage-associated molecules: (i) a group of PGE2-inducible genes, (ii) genes that promote inflammation and are suppressed by PGE2, and (iii) a group of genes not suppressed by PGE2. Collectively, our findings reveal the hitherto unknown immune regulatory system by PGE2 and damage-associated molecules, which may have clinical implications in inflammation and cancer.
    Mesh-Begriff(e) Animals ; Cell Line ; Cell Line, Tumor ; Cyclooxygenase 2/metabolism ; Dinoprostone/metabolism ; Dogs ; Gene Expression/genetics ; Inflammation/metabolism ; Macrophages/metabolism ; Mice ; RAW 264.7 Cells ; RNA, Messenger/metabolism ; Tumor Necrosis Factor-alpha/metabolism
    Chemische Substanzen RNA, Messenger ; Tumor Necrosis Factor-alpha ; Cyclooxygenase 2 (EC 1.14.99.1) ; Dinoprostone (K7Q1JQR04M)
    Sprache Englisch
    Erscheinungsdatum 2021-04-19
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-87979-1
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel ; Online: The Interferon (IFN) Class of Cytokines and the IFN Regulatory Factor (IRF) Transcription Factor Family.

    Negishi, Hideo / Taniguchi, Tadatsugu / Yanai, Hideyuki

    Cold Spring Harbor perspectives in biology

    2018  Band 10, Heft 11

    Abstract: Interferons (IFNs) are a broad class of cytokines elicited on challenge to the host defense and are essential for mobilizing immune responses to pathogens. Divided into three classes, type I, type II, and type III, all IFNs share in common the ability to ...

    Abstract Interferons (IFNs) are a broad class of cytokines elicited on challenge to the host defense and are essential for mobilizing immune responses to pathogens. Divided into three classes, type I, type II, and type III, all IFNs share in common the ability to evoke antiviral activities initiated by the interaction with their cognate receptors. The nine-member IFN regulatory factor (IRF) family, first discovered in the context of transcriptional regulation of type I IFN genes following viral infection, are pivotal for the regulation of the IFN responses. In this review, we briefly describe cardinal features of the three types of IFNs and then focus on the role of the IRF family members in the regulation of each IFN system.
    Mesh-Begriff(e) Animals ; DNA ; Gene Expression Regulation/physiology ; Humans ; Interferon Regulatory Factors/genetics ; Interferon Regulatory Factors/metabolism ; Interferons/genetics ; Interferons/metabolism
    Chemische Substanzen Interferon Regulatory Factors ; DNA (9007-49-2) ; Interferons (9008-11-1)
    Sprache Englisch
    Erscheinungsdatum 2018-11-01
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ISSN 1943-0264
    ISSN (online) 1943-0264
    DOI 10.1101/cshperspect.a028423
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; Online: The impact of damage-associated molecules released from canine tumor cells on gene expression in macrophages

    Shotaro Eto / Hideyuki Yanai / Sho Hangai / Daiki Kato / Ryohei Nishimura / Takayuki Nakagawa

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Band 13

    Abstract: Abstract Dying or damaged cells that are not completely eradicated by the immune system release their intracellular components in the extracellular space. Aberrant exposure of the damage-associated molecules to the immune system is often associated with ... ...

    Abstract Abstract Dying or damaged cells that are not completely eradicated by the immune system release their intracellular components in the extracellular space. Aberrant exposure of the damage-associated molecules to the immune system is often associated with inflammation and cancer pathogenesis. Thus, elucidating the role of damage-associated molecules in inducing sterile immune responses is crucial. In this study, we show that prostaglandin E2 (PGE2) is produced in the supernatants from several types of canine necrotic tumor cell lines. Inhibition of PGE2 production by indomethacin, a potent inhibitor of cyclooxygenase (COX) enzymes, induces the expression of tumor necrosis factor (Tnf) mRNA in the necrotic tumor cell supernatants. These results comply with the previous observations reported in mouse cell lines. Furthermore, comprehensive ribonucleic acid-sequencing (RNA-seq) analysis revealed that three categories of genes were induced by the damage-associated molecules: (i) a group of PGE2-inducible genes, (ii) genes that promote inflammation and are suppressed by PGE2, and (iii) a group of genes not suppressed by PGE2. Collectively, our findings reveal the hitherto unknown immune regulatory system by PGE2 and damage-associated molecules, which may have clinical implications in inflammation and cancer.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 616
    Sprache Englisch
    Erscheinungsdatum 2021-04-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  10. Artikel ; Online: Acidic extracellular pH drives accumulation of N1-acetylspermidine and recruitment of protumor neutrophils.

    Kato, Miki / Maeda, Keisuke / Nakahara, Ryuichi / Hirose, Haruka / Kondo, Ayano / Aki, Sho / Sugaya, Maki / Hibino, Sana / Nishida, Miyuki / Hasegawa, Manami / Morita, Hinano / Ando, Ritsuko / Tsuchida, Rika / Yoshida, Minoru / Kodama, Tatsuhiko / Yanai, Hideyuki / Shimamura, Teppei / Osawa, Tsuyoshi

    PNAS nexus

    2023  Band 2, Heft 10, Seite(n) pgad306

    Abstract: An acidic tumor microenvironment plays a critical role in tumor progression. However, understanding of metabolic reprogramming of tumors in response to acidic extracellular pH has remained elusive. Using comprehensive metabolomic analyses, we ... ...

    Abstract An acidic tumor microenvironment plays a critical role in tumor progression. However, understanding of metabolic reprogramming of tumors in response to acidic extracellular pH has remained elusive. Using comprehensive metabolomic analyses, we demonstrated that acidic extracellular pH (pH 6.8) leads to the accumulation of N1-acetylspermidine, a protumor metabolite, through up-regulation of the expression of spermidine/spermine acetyltransferase 1 (
    Sprache Englisch
    Erscheinungsdatum 2023-10-10
    Erscheinungsland England
    Dokumenttyp Journal Article
    ISSN 2752-6542
    ISSN (online) 2752-6542
    DOI 10.1093/pnasnexus/pgad306
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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